Xiao X-G, Zu H-G, Li Q-G, Huang P
The Burn and Plastic Department, The First Affiliated Hospital of the University of Henan Science and Technology, Henan, China.
Eur Rev Med Pharmacol Sci. 2016;20(3):528-36.
Patients with severe burns often develop acute lung injury (ALI), systemic inflammatory response syndrome (SIRS) often complicates with ALI. Sivelestat sodium hydrate is an effective drug against ALI. However, the mechanisms of this beneficial effect are still poorly understood. In the current study, we evaluate the effects of sivelestat sodium hydrate on systemic and local inflammatory parameters (neutrophil elastase [NE], interleukin [IL]-8, matrix metalloproteinase [MMP] 2 and 9) in a rat model of severe burns and ALI. And to analyze the correlations between expression of NE and IL-8 and acute lung injury.
48 Sprague-Dawley (SD) rats were divided into 3 groups: normal control group, severe burns injury group and severe burns treated with sivelestat sodium hydrate group (SSI). The lung water content and PaO2 were detected in each group. Pathological manifestations in each group were observed for pathology scoring in SD rats with acute lung injury. ELISA was used for detecting expression of NE and IL-8 in serum and BAL specimens of SD rats in each group. RT-PCR was used to detect mRNA expression of NE and IL-8 in lung tissues of each group. Western blotting was used for detecting protein expression of MMP-2 and MMP-9 in lung tissues of each group. SPSS 18.0 was used for statistical analysis.
The PaO2 was significantly increased after sivelestat sodium hydrate intravenous injection. Pathological score and water content of lung tissue were significantly decreased in SSI group compared with severe burns injury group, slightly higher than that normal control group. NE and IL-8 levels significantly decreased in serum, BAL and lung tissue specimens after sivelestat sodium hydrate intravenous injection; Expression of MMP-2 and MMP-9 were significantly up-regulated in severe burns group and showed no significantly changed after sivelestat sodium hydrate intravenous injection.
In a rat model of severe burns and ALI, administration of sivelestat sodium hydrate improved symptoms of ALI and significantly decreased inflammatory parameters NE and IL-8.
严重烧伤患者常发生急性肺损伤（ALI），全身炎症反应综合征（SIRS）常与ALI并发。水合西维来司他钠是一种治疗ALI的有效药物。然而，这种有益作用的机制仍不清楚。在本研究中，我们评估了水合西维来司他钠对严重烧伤和ALI大鼠模型全身和局部炎症参数（中性粒细胞弹性蛋白酶[NE]、白细胞介素[IL]-8、基质金属蛋白酶[MMP]2和9）的影响。并分析NE和IL-8表达与急性肺损伤之间的相关性。
将48只Sprague-Dawley（SD）大鼠分为3组：正常对照组、严重烧伤组和水合西维来司他钠治疗严重烧伤组（SSI）。检测每组大鼠的肺含水量和动脉血氧分压（PaO2）。观察每组大鼠的病理表现并进行急性肺损伤病理评分。采用酶联免疫吸附测定（ELISA）法检测每组SD大鼠血清和支气管肺泡灌洗（BAL）标本中NE和IL-8的表达。采用逆转录-聚合酶链反应（RT-PCR）法检测每组大鼠肺组织中NE和IL-8的mRNA表达。采用蛋白质印迹法检测每组大鼠肺组织中MMP-2和MMP-9的蛋白表达。使用SPSS 18.0软件进行统计分析。
静脉注射水合西维来司他钠后，PaO2显著升高。与严重烧伤组相比，SSI组肺组织病理评分和含水量显著降低，但略高于正常对照组。静脉注射水合西维来司他钠后，血清、BAL和肺组织标本中NE和IL-8水平显著降低；严重烧伤组MMP-2和MMP-9表达显著上调，静脉注射水合西维来司他钠后无显著变化。
在严重烧伤和ALI大鼠模型中，给予水合西维来司他钠可改善ALI症状，并显著降低炎症参数NE和IL-8。
